Recent advances in cellular immunology have revolutionized our understanding of antigen processing and presentation. UBIVAC, LLC, has an exclusive option on technology (patent pending) that exploits these developments that was developed by Dr. Hong-Ming Hu. Further, the founders of UBIVAC (Drs. Hu and Fox) and their collaborators have investigated additional treatment combinations that can significantly augment the therapeutic efficacy of vaccines. The combination of these strategies with this vaccine technology (DRibbles) in preclinical animal models further increased priming/expansion of tumor-specific T cells and provided a significant survival advantage for the DRibble vaccine strategy. Based on the data generated in UBIVAC's Phase I SBIR, a pilot Clinical Trial of Autologous NSCLC DRibbles was initiated (R21-CA123864). This Investigator-initiated trial just opened and autologous DRibble vaccine has been successfully made for the first eligible patient. UBIVAC, LLC, has one candidate NSCLC cell line (adenocarcinoma) that over expresses a large number of genes in common with seven other NSCLC cell lines screened, grows well and is a good producer of supernatant DRibbles. Before this SBIR Phase II award is initiated, UBIVAC will use the same criteria listed above to identify a second cell line (of squamous origin) for production of DRibbles. In Aim 1 UBIVAC will generate a master cell bank (MCB) for each cell line, test the MCBs for sterility, generate WCBs and optimize DRibble production using CMC specifications from the FDA-approved autologous NSCLC DRibble IND and produce sufficient vaccine to complete the 48 patient trial. Aim 2 will conduct a randomized phase II trial of docetaxel and allogeneic NSCLC DRibble vaccine combined with either GM-CSF or imiquimod (DRibble Plus) Aim 3 will evaluate the humoral immune response induced by Universal NSCLC DRibble Plus vaccine. It will also investigate whether vaccination reduces the number of circulating tumor cells (CTC), a biomarker that has the potential to be a surrogate for clinical response. UBIVAC, LLC has a letter of intent that could provide 2 to 50 million dollars to support the commercial development of DRibble technology if the proposed phase II SBIR study is successful. To help guide this transition UBIVAC has assembled an advisory board that includes a successful president/CEO with more than 40 years Pharma experience;a physician- scientist with large Pharma oncology experience who served as Global Head Vaccines &Immunomodulatory Agents;and the managing Director of Northwest Technology Ventures. Taken together, UBIVAC has the critical elements, compelling preclinical data, Individuals with substantial clinical, translational research, business and venture experience, a well designed randomized phase II study and cutting edge monitoring strategies that hold great promise to make a difference in the lives of patients with NSCLC, and the experience to get this agent to market. PUBLIC HEALTH RELEVANCE: Successful completion of the randomized Phase II clinical trial of UBIVAC's two promising NSCLC Dribble Plus vaccines (DPV-1 + GM-CSF or imiquimod) will allow UBIVAC to "pick-the-winner", arrange funding and/or a strategic partner and provide a compelling argument to move the lead product forward into a randomized Phase III clinical trial for advanced NSCLC.